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The effects of dodecyl maltoside and sodium dodecyl sulfate surfactants on the stability and aggregation of recombinant interferon Beta-1b

机译:十二烷基麦芽糖苷和十二烷基硫酸钠表面活性剂对重组干扰素β-1b稳定性和聚集的影响

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摘要

Aggregation often occurs during manufacturing and storage of protein drugs. Detergents such as sodium dodecyl sulfate are commonly used to prevent aggregation but need to be eliminated before final formulation for safety reasons. We studied the ability of dodecylmaltoside (DDM), a nontoxic alkyl saccharide surfactant, to reduce aggregation and increase the stability of interferon beta-1b (IFN)-β-1b. An increase of 8°C in the Tm of IFN-β-1b was observed when 0.1% of DDM was present in the protein solution. The absorption of DDM on hydrophobic surfaces of IFN-β-1b enables the surface to become hydrophilic and non-ionic, and increases the stability of the protein. 0.1% DDM also results in a 62% increase in helical and a 25% decrease in β-sheet structures. 0.1% DDM not only suppresses aggregate formation but also improves IFN-β-1b solubilization. Furthermore, we have showed the protective effect of DDM on the anti-viral activity of IFN-β-1b in solution.
机译:聚集经常发生在蛋白质药物的制造和储存过程中。洗涤剂(如十二烷基硫酸钠)通常用于防止聚集,但出于安全原因,在最终配制之前必须将其清除。我们研究了十二烷基麦芽糖苷(DDM)(一种无毒的烷基糖类表面活性剂)减少聚集和增加干扰素β-1b(IFN)-β-1b稳定性的能力。当蛋白质溶液中存在0.1%的DDM时,可观察到IFN-β-1b的Tm升高8°C。 DDM在IFN-β-1b疏水表面上的吸收使表面成为亲水和非离子表面,并增加了蛋白质的稳定性。 0.1%的DDM还会导致螺旋线增加62%,β-折叠结构减少25%。 0.1%DDM不仅抑制聚集体形成,而且改善IFN-β-1b的溶解性。此外,我们已经显示了DDM对溶液中IFN-β-1b的抗病毒活性的保护作用。

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